This research proposal is designed to examine the effects of partial agonists on the endocytosis and degradation of the beta- adrenergic receptor. Partial agonists, such as salmeterol, are known to play a role in the treatment of asthma, and it will be beneficial to examine their roles in receptor degradation. The hypothesis is that agonists with varying efficacies will cause various levels of receptor degradation. To examine this, the endocytic and recycling rate constants for each partial agonist will be determined, as well as receptor degradation rates. These studies will utilize radioligand binding assays and receptor purification techniques. Also this proposal will examine whether the levels of beta-arrestin and/or G-protein coupled receptor kinases have any effect on endocytosis induced by partial agonists. This will involve transfecting HEK 293 cells with plasmid DNA for arrestin and GRK, as well as the beta-receptor, followed by measuring the receptor endocytic rate constants induced by partial agonists. The third aim for this study will examine agonists with high affinity and their effects on receptor internalization. ELISA assays will determine surface receptor levels after partial agonist treatment and confocal microscopy will determine whether receptors are entering endosomes after agonist treatment.